The most common inherited disorder causing blindness in man is retinitis pigmentosa, a disease or family of diseases in which the rod photoreceptors of the retina break down slowly and progressively over a period of years, and pigment epithelial cells move into degenerating retina. Similar inherited diseases are known in several laboratory animals. The research proposed here is to study the effects of three point mutations that affect the retina. These animal models are the RCS rat and two cerebellar mutant mice, nervous and Purkinje cell degeneration. The research concerns the interaction of photoreceptor cells and pigment epithelial cells in normal animals and in mutants and the specific mechanisms of photoreceptor degeneration in the mutants. The tools that will be brought to bear on several problems in each of these mutants and control animals are those of formal genetics, light and electron microscopy, autoradiography, environmental lighting modification, timing of rod outer segment disc shedding in relation to cyclic lighting and the analysis of experimental chimeras. The objective will be to gain insight into basic cellular mechanisms that are vulnerable to various genetic defects so that when eyes of early stages of retinitis pigmentosa become available, we will have a better understanding of cytopathological principals regarding photoreceptor degeneration and of possible therapeutic measures.